Caracterização físico-química do fármaco antichagásico benznidazol

Currently, benznidazole (BNZ) is a unique therapeutic alternative available in Brazil to treat Chagas disease. Despite its traditional medical use, little is known about the chemical nature of this drug. A detailed study of the physicochemical properties of BNZ was performed using multiple assays. Thermal, diffractometric, morphological and reological drug profiles were obtained. The partition coefficient and solubility results allowed this drug to be classified as a class IV drug according to the biopharmaceutical classification system. This information will be useful for the development of more effective BNZ formulations and for establishing the quality profile of BNZ

Pervasive gaps in Amazonian ecological research

Biodiversity loss is one of the main challenges of our time,1,2 and attempts to address it require a clear un derstanding of how ecological communities respond to environmental change across time and space.3,4 While the increasing availability of global databases on ecological communities has advanced our knowledge of biodiversity sensitivity to environmental changes,5–7 vast areas of the tropics remain understudied.8–11 In the American tropics, Amazonia stands out as the world’s most diverse rainforest and the primary source of Neotropical biodiversity,12 but it remains among the least known forests in America and is often underrepre sented in biodiversity databases.13–15 To worsen this situation, human-induced modifications16,17 may elim inate pieces of the Amazon’s biodiversity puzzle before we can use them to understand how ecological com munities are responding. To increase generalization and applicability of biodiversity knowledge,18,19 it is thus crucial to reduce biases in ecological research, particularly in regions projected to face the most pronounced environmental changes. We integrate ecological community metadata of 7,694 sampling sites for multiple or ganism groups in a machine learning model framework to map the research probability across the Brazilian Amazonia, while identifying the region’s vulnerability to environmental change. 15%–18% of the most ne glected areas in ecological research are expected to experience severe climate or land use changes by 2050. This means that unless we take immediate action, we will not be able to establish their current status, much less monitor how it is changing and what is being lostinfo:eu-repo/semantics/publishedVersio

Pervasive gaps in Amazonian ecological research

Biodiversity loss is one of the main challenges of our time,1,2 and attempts to address it require a clear understanding of how ecological communities respond to environmental change across time and space.3,4 While the increasing availability of global databases on ecological communities has advanced our knowledge of biodiversity sensitivity to environmental changes,5,6,7 vast areas of the tropics remain understudied.8,9,10,11 In the American tropics, Amazonia stands out as the world's most diverse rainforest and the primary source of Neotropical biodiversity,12 but it remains among the least known forests in America and is often underrepresented in biodiversity databases.13,14,15 To worsen this situation, human-induced modifications16,17 may eliminate pieces of the Amazon's biodiversity puzzle before we can use them to understand how ecological communities are responding. To increase generalization and applicability of biodiversity knowledge,18,19 it is thus crucial to reduce biases in ecological research, particularly in regions projected to face the most pronounced environmental changes. We integrate ecological community metadata of 7,694 sampling sites for multiple organism groups in a machine learning model framework to map the research probability across the Brazilian Amazonia, while identifying the region's vulnerability to environmental change. 15%–18% of the most neglected areas in ecological research are expected to experience severe climate or land use changes by 2050. This means that unless we take immediate action, we will not be able to establish their current status, much less monitor how it is changing and what is being lost

Hidrossolubilização e avaliação biológica do fármaco antichagásico benznidazol.

Benznidazol é um fármaco empregado para o tratamento da doença de Chagas, sendo o único recurso terapêutico disponível no Brasil para combater esta grave doença. Estudos mostram que apesar de sua efetividade pré-clínica, o benznidazol apresenta baixa solubilidade aquosa e errática biodisponibilidade, além de importantes efeitos colaterais que levam ao abandono da terapêutica, especialmente na fase crônica da doença. Desse modo, este trabalho propôs-se a desenvolver formas farmacêuticas sólidas a base de benznidazol, capazes de favorecer sua solubilidade e velocidade de dissolução e minimizar os problemas de biodisponibilidade relatados. Realizou-se, inicialmente, um estudo de pré-formulação através de uma detalhada investigação sobre as propriedades físico-químicas do benznidazol até então desconhecidas. Dados precisos de solubilidade, velocidade intrínseca de dissolução, tamanho e superfície de partícula e permeabilidade foram determinados. Uma pesquisa das possíveis formas polimórficas do benznidazol foi conduzida em várias condições de cristalização, sem que tenham sido detectadas formas meta-estáveis. No estudo de compatibilidade fármaco- excipiente, o benznidazol mostrou-se compatível com excipientes farmacêuticos de diferentes classes farmacotécnicas, apresentando-se incompatibilidade térmica apenas com o polímero polietilenoglicol. Durante os estudos de formulação, duas estratégias de solubilização do fármaco foram adotadas: a obtenção de complexos de inclusão utilizando ciclodextrinas inseridos em comprimidos efervescentes e a preparação de microcristais de benznidazol pela técnica de recristalização por mudança de solvente, inseridos em matrizes de comprimidos. As formulações produzidas apresentaram melhorias importantes no perfil de dissolução do fármaco. Os comprimidos contendo microcristais de benznidazol apresentaram o melhor desempenho in vitro, tendo sido selecionados para a realização de estudos de atividade biológica utilizando modelo murino para doença de Chagas. Os resultados in vivo demonstraram uma redução considerável na parasitemia e na mortalidade nos animais infectados, além de importantes incrementos nos percentuais de cura parasitológica, comparados com o tratamento comercial atualmente disponível. Desta forma, o estudo realizado aporta promissoras perspectivas de avanço na terapêutica antichagásica.The benznidazole is a drug used clinically for the treatment of Chagas disease, the only therapeutic option available in Brazil to combat this serious disease. Studies show that despite its pre-clinical effectiveness, the benznidazole has low water solubility and bioavailability, and important side effects that lead to abandonment of therapy, especially in the chronic phase. Thus, this work seeks to develop solid dosage forms with benznidazole to favor its solubility and dissolution rate in order to minimize the problems of bioavailability reported. Initially, a study of pre-formulation was held through a detailed investigation into the physico-chemical properties of benznidazole hitherto unknown. Accurate solubility, intrinsic dissolution rate, particle size and surface area and permeability were determined. A survey of the possible polymorphic forms of the benznidazole was conducted at several crystallization conditions, without having been detected meta-stable forms. In the compatibility study performed against different pharmaceutical excipients, the benznidazole was compatible with pharmaceutical excipients of different functional classes presenting thermal incompatibility just with the polymer polyethylene glycol. During the formulation studies, two strategies of drug solubilisation were adopted: the production of inclusion complex using cyclodextrin in effervescent tablets and the preparation of benznidazole microcristals by solvent change precipitation procedure and its incorporation in tablets matrices. The dosage form produced presented improvements in drug dissolution behavior. The BNZ tablets containing microcristals by solvent change method presented the best performance in vitro and were selected to the biologic studies for Chagas disease. The in vivo results showed a considerable reduction in parasitemia and mortality of infected animals. Also, important progresses in parasitological cure compare with commercial treatment available were achieved. Therefore, this study brings promising perspectives in the therapeutic of Chagas disease

Polymorphic screen and drug–excipient compatibility studies of the antichagasic benznidazole.

The purpose of this study was to investigate the polymorphism and compatibility of benznidazole (BNZ), a drug used in the treatment of Chagas disease. This drug was subjected to a polymorphic screen using a number of solvents and precipitation procedures to explore the possible existence of different crystal structures of BNZ. The compatibility of BNZ with selected pharmaceutical excipients was evaluated in binary mixtures, in a ratio of 1:1 (w/w). These results were then analyzed with a variety of techniques, including differential scanning calorimetry, Fourier transform infrared spectroscopy, and X-ray powder diffractometry. No polymorphic forms of BNZ were detected despite some observed changes in the DSC profile. The thermal data indicate interaction of the drug with excipients hydroxyethylcellulose, polyethylene glycol, and hydroxypropyl-b-cyclodextrin. Additional studies using infrared spectroscopy confirm the incompatibility of BNZ with only the polyethylene glycol. This excipient should not be used in the development of solid dosage forms containing BNZ

Development of effervescent tablets containing benznidazole complexed with cyclodextrin.

Objectives: Benznidazole (BNZ), the primary chemotherapy agent used to treat Chagas disease, has poor aqueous solubility, which results in low bioavailability. The purpose of this work was to develop stable effervescent tablets using an inclusion complex of BNZ with cyclodextrin (CD). Method: In the first phase, different CDs were evaluated according to their ability to improve the aqueous solubility of BNZ. Then, inclusion complexes of BNZ in the solid state were produced by the kneading method and the complexes were evaluated using several physical–chemical assays. Finally, effervescent tablets were prepared according to a complete 32 factorial design. The effects of the concentration of CD and effervescent mixture on the dissolution rate and physical stability of tablets were evaluated. Key findings: Hydroxypropyl-b-cyclodextrin produced the greatest improvement in the aqueous solubility of BNZ, almost 20-times greater than the water system. Solid systems produced with BNZ and CD showed physical–chemical interactions and increased the drug dissolution rate, suggesting the formation of a true solid inclusion complex. Moreover, the effervescent matrix of the tablets was effective in improving the dissolution behaviour of BNZ complexed with CD. Conclusions: Effervescent tablets produced using an inclusion complex of BNZ with CD suggest a possible improvement in the bioavailability of BNZ, and this could represent a relevant advance in Chagas therapy

Benznidazole microcrystal preparation by solvent change precipitation and in vivo evaluation in the treatment of Chagas disease.

Benznidazole (BNZ) is traditionally used to treat Chagas disease. Despite its common use, BNZ has a poor water solubility and a variable bioavailability. The purpose of this study was to prepare BNZ microcrystals by solvent change precipitation and to study the effects of BNZ micronisation on therapeutic efficiency using a murine model of Chagas disease. The solvent change precipitation procedure was optimised in order to obtain stable and homogeneous particles with a small particle size, high yield and fast dissolution rate. The thermal and crystallographic analysis showed no polymorphic change in the microcrystals, and microscopy confirmed a significant reduction in particle size. A marked improvement in the drug dissolution rate was observed for micronised BNZ particles and BNZ tablets in comparison with untreated BNZ and commercial Rochagan_. In vivo studies showed a significant increase in the therapeutic efficacy of the BNZ microparticles, corroborating the dissolution results

Characterisation of microbial attack on archaeological bone

As part of an EU funded project to investigate the factors influencing bone preservation in the archaeological record, more than 250 bones from 41 archaeological sites in five countries spanning four climatic regions were studied for diagenetic alteration. Sites were selected to cover a range of environmental conditions and archaeological contexts. Microscopic and physical (mercury intrusion porosimetry) analyses of these bones revealed that the majority (68%) had suffered microbial attack. Furthermore, significant differences were found between animal and human bone in both the state of preservation and the type of microbial attack present. These differences in preservation might result from differences in early taphonomy of the bones. © 2003 Elsevier Science Ltd. All rights reserved